RECORD: Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00379769

First received: September 21, 2006

Last updated: May 3, 2013

Last verified: May 2013

History of Changes

Results First Received: August 24, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Diabetes Mellitus, Type 2
Interventions:	Drug: Rosiglitazone Drug: Sulfonylurea Drug: Metformin

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The RECORD study ran from April 2001 through December 2008. Results are presented in the non-re-adjudicated outcome measures (OMs). An independent patient-level re-adjudication of mortality, non-fatal myocardial infarction, and non-fatal stroke began on January 2011 and ran through March 2012. The results are presented in the re-adjudicated OMs.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
RSG in Addition to Background MET	Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET	Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU	Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU	Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Participant Flow: Overall Study

	RSG in Addition to Background MET	SU in Addition to Background MET	RSG in Addition to Background SU	MET in Addition to Background SU
STARTED	1117	1105	1103	1122
COMPLETED	939	906	896	892
NOT COMPLETED	178	199	207	230
Death	57	67	54	72
Adverse Event	5	8	10	11
Lost to Follow-up	29	29	25	26
Withdrawal by Subject	46	56	72	70
Moved to survival status follow-up only	27	25	32	36
Participant moved	3	2	3	3
Poor compliance	3	2	2	1
Prohibited glucose lowering medication	0	3	0	1
Site closed	4	4	4	8
Entry criteria violation	0	0	1	1
Participant did not take study drug	0	0	1	0
Physician Decision	2	2	1	1
Participant completed study at visit 27	1	0	0	0
Personal reasons	1	0	0	0
Risk of heart failure	0	1	0	0
Investigator refused to log temperature	0	0	1	0
Reason unspecified	0	0	1	0

Baseline Characteristics

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Reporting Groups

	Description
RSG in Addition to Background MET	Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET	Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU	Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU	Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Total	Total of all reporting groups

Baseline Measures

	RSG in Addition to Background MET	SU in Addition to Background MET	RSG in Addition to Background SU	MET in Addition to Background SU	Total
Number of Participants [units: participants]	1117	1105	1103	1122	4447
Age [units: years] Mean ± Standard Deviation	57.0 ± 8.02	57.2 ± 8.14	59.8 ± 8.26	59.7 ± 8.23	58.4 ± 8.27
Gender [units: participants]
Female	516	521	562	554	2153
Male	601	584	541	568	2294
Race/Ethnicity, Customized [units: participants]
White	1105	1087	1095	1112	4399
Black	3	6	2	3	14
Oriental	4	2	5	7	18
Aboriginal	1	0	0	0	1
African	1	0	0	0	1
Asian	1	2	1	0	4
Egyptian	1	0	0	0	1
Gipsy	1	0	0	0	1
Indian	0	1	0	0	1
Maori	0	1	0	0	1
Middle East Hible	0	1	0	0	1
Pacific Islander	0	1	0	0	1
Polynesian	0	1	0	0	1
Sri Lankan	0	2	0	0	2
Tahitian	0	1	0	0	1

Outcome Measures

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1. Primary:

Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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2. Primary:

Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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3. Primary:

Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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4. Primary:

Independent Re-adjudication Outcome: Number of Participants With a First Occurence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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5. Primary:

Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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6. Primary:

Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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7. Primary:

Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

Show Outcome Measure 7

8. Primary:

Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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9. Primary:

Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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10. Primary:

Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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11. Secondary:

Number of Participants With Cardiovascular Events and All-cause Deaths [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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12. Secondary:

Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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13. Secondary:

Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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14. Secondary:

Number of Participants With CV/Microvascular Events [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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15. Secondary:

Number of Participants With Glycaemic Failure Events [ Time Frame: Baseline through to end of randomised dual therapy ]

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16. Secondary:

Number of Participants With Addition of Third Oral Agent/Switch to Insulin [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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17. Secondary:

The Number of Participants Starting Insulin at Any Time During the Study [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

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18. Secondary:

Model Adjusted Change From Baseline in HbA1c at Month 60 [ Time Frame: Baseline and Month 60 of randomised dual therapy treatment period ]

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Measure Type	Secondary
Measure Title	Model Adjusted Change From Baseline in HbA1c at Month 60
Measure Description	Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value.
Time Frame	Baseline and Month 60 of randomised dual therapy treatment period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who were treated with at least one dose of study medication

Reporting Groups

	Description
RSG in Addition to Background MET	Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET	Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU	Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU	Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.

Measured Values

	RSG in Addition to Background MET	SU in Addition to Background MET	RSG in Addition to Background SU	MET in Addition to Background SU
Number of Participants Analyzed [units: participants]	1096	1079	1073	1079
Model Adjusted Change From Baseline in HbA1c at Month 60 [units: Percent] Mean ± Standard Error	-0.14 ± 0.035	0.17 ± 0.042	-0.24 ± 0.039	-0.10 ± 0.039

No statistical analysis provided for Model Adjusted Change From Baseline in HbA1c at Month 60

19. Secondary:

Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

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20. Secondary:

Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

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21. Secondary:

Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

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22. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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23. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Show Outcome Measure 23

24. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholersterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

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25. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

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26. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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27. Secondary:

Model Adjusted Change From Baseline in Body Weight at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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28. Secondary:

Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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29. Secondary:

Model Adjusted Change From Baseline in Waist Circumference at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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30. Secondary:

Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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31. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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32. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

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33. Secondary:

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60 [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

Show Outcome Measure 33

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

Publications:

Home PD, Pocock SJ, Beck-Nielsen H et al. The Lancet 2009; 373:2125-2135.

Publications automatically indexed to this study:

MacDonald MR, Petrie MC, Home PD, Komajda M, Jones NP, Beck-Nielsen H, Gomis R, Hanefeld M, Pocock SJ, Curtis PS, McMurray JJ. Incidence and prevalence of unrecognized myocardial infarction in people with diabetes: a substudy of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) study. Diabetes Care. 2011 Jun;34(6):1394-6. Epub 2011 May 11.

Komajda M, Curtis P, Hanefeld M, Beck-Nielsen H, Pocock SJ, Zambanini A, Jones NP, Gomis R, Home PD; RECORD Study Group. Effect of the addition of rosiglitazone to metformin or sulfonylureas versus metformin/sulfonylurea combination therapy on ambulatory blood pressure in people with type 2 diabetes: a randomized controlled trial (the RECORD study). Cardiovasc Diabetol. 2008 Apr 24;7:10.

Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ; RECORD Study Group. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. N Engl J Med. 2007 Jul 5;357(1):28-38. Epub 2007 Jun 5.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00379769 History of Changes
Other Study ID Numbers:	BRL-049653/231
Study First Received:	September 21, 2006
Results First Received:	August 24, 2009
Last Updated:	May 3, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

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